This proposal requests support for a continuation of a project initiated by a Program Project grant (AG 04948). The study utilizes a systematically derived and maintained genetically heterogeneous stock of mice in a combined longitudinal and cross-sectional design which covers the lifespan of the animals. Animals will be measured on a wide variety of age-related phenotypes from a number of domains relevant to gerontology. These include behavior, free-radicals, homeostasis, immunology, pathology and physiology. Multivariate analyses will examine the structural relationships among variables within and between these domains, and in changes taking place over chronological age, and will be employed in survival analyses. The longitudinal study involves two-generation families. Quantitative genetic analyses based on relationships of parent and offspring, siblings, cousins, aunt/uncle and niece/nephew will generate estimates of the genetic and environmental contributions to the variances of the individual phenotypes and to linear composites derived from the multivariate analyses, and to the lifespan changes in these single and composite phenotypes.